Summary A relationship between dementia, including Alzheimer's disease (AD) has been well documented; however, the causality of this relationship and the underlying mechanisms remain uncertain. Our long-term goal is to leverage transgenic mouse models of AD to investigate this relationship, with particular attention paid to the interplay afferent and efferent auditory pathways in the cochlea and brainstem. We hypothesize that diminished cholinergic efferents in AD mutants contribute to accelerated hearing loss, peripheral damage, and suprathreshold hearing dysfunction. We propose to begin work toward our goal with one Specific Aim: Characterize peripheral and central hearing dysfunction related to efferent dysfunction and anatomical correlates in mouse models of AD. Techniques utilized in the parent grant will be applied to two mutant models of human AD neuropathology to lay the framework for future investigations elucidating the role of auditory system pathology in the progression of AD.